The patch-clamp technique is the central tool for characterizing ion channel function. For functional genomics and for drug discovery, the ability to perform high-throughput (HTS) patch clamp recordings is urgently needed. We propose to develop an enabling technology for HTS recordings by integrating a high-performance patch-clamp amplifier into a single monolithic integrated circuit. Our goal is to develop a chip containing multiple amplifiers and to develop the associated interfacing electronics. High-density assembly of our chips will allow as many as 384 automated patch-amplifiers to be matched to a corresponding array of planar patch-clamp electrodes allowing massively-parallel patch-clamp measurements. PUBLIC HEALTH RELEVANCE: Relevance The activity of ion channels is responsible for very many physiological functions and underlie many pathophysiologies, ranging from epilepsy and cardiac arrhythmias to Cystic Fibrosis and deafness. The characterization of ion channel function, and the development of drugs that modify this function, urgently requires new instrumentation that allows "high throughput" measurements.